Lack of interaction between metoclopramide and morphine in vitro and in mice.
1. This study examined interactions via common metabolism or via common pharmacodynamic pathways between frequently co-prescribed metoclopramide (a prokinetic) and morphine (an opioid analgesic). 2. In human liver microsomes, morphine 3-glucuronide and morphine 6-glucuronide formation had V(max) estimates of 6.2 +/- 0.07 and 0.75 +/- 0.01 (nmole min(-1) mg(-1) protein) and K(m) estimates of 1080 +/- 37 and 665 +/- 55 (microM), respectively. The in vitro K(i) for morphine 3-glucuronide formation in the presence of metoclopramide in human liver microsomes or recombinant uridine diphosphoglucuronosyltransferase 2B7 predicted a lack of in vivo interaction. 3. Morphine (2 mg kg(-1) subcutaneously) delayed gastrointestinal meal transit in mice, metoclopramide (10 mg kg(-1) subcutaneously) had no effect on meal transit, and metoclopramide did not alter this effect of morphine. 4. Morphine (2 or 5 mg kg(-1) subcutaneously) was antinociceptive in mice (hot plate test) and metoclopramide (10 mg kg(-1) subcutaneously) did not alter the antinociceptive effects of morphine. 5. Together, the data suggest a lack of interaction between morphine and metoclopramide.
Ung
D
D
Pharmaceutical Sciences, Temple University, Philadelphia, PA 19140, USA.
Cowan
A
A
Parkman
H P
HP
Nagar
S
S
D000701:Analgesics, Opioid / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D018492:Dopamine Antagonists / Q000378:metabolism* / Q000494:pharmacology; D004347:Drug Interactions; D005772:Gastrointestinal Transit / Q000187:drug effects / Q000502:physiology; D006801:Humans; D007700:Kinetics; D008297:Male; D008787:Metoclopramide / Q000378:metabolism* / Q000494:pharmacology; D051379:Mice; D008862:Microsomes, Liver / Q000378:metabolism; D009020:Morphine / Q000378:metabolism* / Q000494:pharmacology
D000701:Analgesics, Opioid; D018492:Dopamine Antagonists; D009020:Morphine; D008787:Metoclopramide